Hypertension refers to an excessive increase in either of the following blood pressures: systolic blood pressure; i.e., maximum blood pressure as measured when the heart contracts to pump blood into arteries; and diastolic blood pressure; i.e., minimum blood pressure as measured when the heart is dilated and filled with blood. According to the World Health Organization (WHO), hypertension is defined as a maximum blood pressure (a systolic blood pressure) of higher than 140 mmHg, or a minimum blood pressure (a diastolic blood pressure) of higher than 90 mmHg (Non-Patent Document 1). Hypertension is classified into two types: essential hypertension, which cannot be attributed to any particular cause, and secondary hypertension, resulting from an apparent cause. Essential hypertension has been reported to account for 90% or more of all hypertensive cases. Essential hypertension, which often develops after middle age and becomes chronic, is a leading cause of death worldwide, since it is a condition of high prevalence, causes damage to major organs (e.g., the brain, the heart, and the kidneys), and closely relates the course of other arteriosclerotic diseases.
Generally employed hypertension therapeutic agents include (1) a calcium antagonist, (2) an angiotensin-converting enzyme inhibitor, (3) an angiotensin II receptor antagonist, (4) a diuretic, and (5) a sympatholytic agent. However, each of these hypertension therapeutic agents exhibits side effects, and may fail to be administered to some patients. Therefore, demand has arisen for a hypertension therapeutic agent based on a new mechanism.
(7α)-21-[4-[(Diethylamino)methyl]-2-methoxyphenoxy]-7-methyl-19-norpregna-1,3,5(10)-trien-3-ol or a pharmaceutically acceptable salt thereof (see the following structural formula (1), a citric acid salt of the compound may be abbreviated as “TAS-108”) has strong affinity to estrogen receptor (ER), and is known as an excellent breast cancer therapeutic agent (Patent Document 1 and Non-Patent Document 2).
[F1]

This compound is also considered useful as a therapeutic agent for pulmonary hypertension or osteoporosis (see, for example, Patent Document 1). Pulmonary hypertension is a disease in which it is difficult for blood to pass through narrowed peripheral arteriolar lumens of blood vessels carrying blood from the heart to the lungs (i.e., pulmonary arteries), resulting in an increase in blood pressure in the pulmonary arteries (pulmonary arterial pressure). Since the right ventricle of the heart, which pumps blood into the pulmonary arteries, cannot endure high pressure, continuously high pulmonary arterial pressure causes deterioration in right ventricular function, leading to right ventricular failure. In general, normal pulmonary arterial pressure is 30 to 15 mmHg (systolic), 8 to 2 mmHg (diastolic), and 18 to 9 mmHg (mean). Therefore, pulmonary hypertension is defined as a systolic pulmonary arterial pressure of 30 mmHg or higher, or a mean pulmonary arterial pressure of 20 mmHg or higher. According to statistics compiled by the Japanese Ministry of Health, Labor and Welfare in 2003, in Japan, the number of patients with primary pulmonary hypertension (see classification of pulmonary hypertension) has been increasing year by year, and was reported to be 637 in 2002. Unlike the case of systemic hypertension, pulmonary hypertension is often complicated with various cardiopulmonary diseases. Pulmonary hypertension which is not associated with such diseases is called primary pulmonary hypertension (PPH), and is designated as a specified disease (i.e., an intractable disease). Thus, pulmonary hypertension completely differs from systemic hypertension in terms of symptoms and definition.
Selective estrogen receptor modulators (SERMs) are a class of chemically synthesized drugs which bind to estrogen receptor α (ERα), and which exhibit both estrogenic (agonistic) effect and anti-estrogenic (antagonistic) effect in an organ-specific manner. Tamoxifen and raloxifene, which are typical SERMs, exhibit agonistic effect on bone tissue and lipid metabolism, and antagonistic effect on mammary tissue. It has been reported that these SERMs can be used for blood pressure control (Patent Documents 2 to 4). However, actual tests have shown that when raloxifene, which is a typical SERM, is administered to postmenopausal hypertensive patients, a systolic blood pressure of 142±13 mmHg is reduced only to 139±10 mmHg (Non-Patent Document 3).    Patent Document 1: WO 99/33859    Patent Document 2: GB Patent No. 2374412    Patent Document 3: WO 2001/26651    Patent Document 4: JP-A-2002-531496    Non-Patent Document 1: J. Hypertens., 1999; 17: 151-183    Non-Patent Document 2: Proceedings of the American Association for Cancer Research Annual Meeting, (March, 2001) Vol. 42, pp. 270    Non-Patent Document 3: Am. J. Cardiol., 2004; 94: 1453-1456